Normal Range of NT-proBNP
For excluding chronic heart failure in ambulatory patients under 75 years, NT-proBNP <125 pg/mL is the recommended threshold, with a 99% negative predictive value. 1
Age-Stratified Normal Reference Values
The normal range for NT-proBNP varies significantly by age and must be interpreted accordingly:
For Excluding Heart Failure (Ambulatory Settings)
- Patients <75 years: NT-proBNP <125 pg/mL excludes chronic heart failure 1
- Acute presentations (emergency department): NT-proBNP <300 pg/mL excludes acute heart failure 1
For Confirming Heart Failure (Age-Adjusted Inclusion Thresholds)
- **Patients <50 years:** >450 pg/mL 2, 1
- Patients 50-75 years: >900 pg/mL 2, 1
- Patients >75 years: >1,800 pg/mL 2, 1
Population-Based Reference Values in Healthy Older Adults
Recent research demonstrates that "normal" NT-proBNP levels in apparently healthy community-dwelling older adults are substantially higher than traditional cutoffs, with 97.5th percentile values reaching 663-824 ng/L in men and 343-2,641 ng/L in women aged 65-80+ years 3. This highlights that the 125 pg/mL cutoff remains appropriate for excluding disease but should not be interpreted as an absolute upper limit of normal in asymptomatic elderly individuals.
Critical Adjustments for Patient-Specific Factors
Obesity (BMI ≥30 kg/m²)
- Reduce the threshold by 20-30% because obesity decreases natriuretic peptide levels 1
- For BNP, use a cutoff of 55 pg/mL in patients with BMI >35 kg/m² 1
Advanced Age (>75 years)
- Increase the threshold by 20-30% because age elevates NT-proBNP levels 1
- Use the higher diagnostic threshold of >1,800 pg/mL for confirming heart failure 2, 1
Atrial Fibrillation
- Increase the threshold by 20-30% because atrial fibrillation independently elevates NT-proBNP levels 1, 4
Renal Insufficiency (eGFR <60 mL/min/1.73m²)
- NT-proBNP levels are significantly elevated in renal dysfunction 2, 1
- Use a threshold of <1,200 pg/mL to exclude heart failure in patients with severe chronic renal failure under 50 years 2, 1
Black Patients
- Reduce the threshold by 20-30% because Black patients typically have lower NT-proBNP levels 1
The "Gray Zone" (300-900 pg/mL)
Patients with NT-proBNP levels between 300-900 pg/mL require careful clinical correlation 2. Even mildly elevated levels in this range are associated with increased risk of death, heart failure, atrial fibrillation, and stroke, regardless of the underlying cause 2. Treat NT-proBNP as a continuous variable rather than a binary test—higher values within the gray zone carry progressively greater risk 2.
Common Pitfalls to Avoid
Non-Heart Failure Causes of Elevated NT-proBNP
Elevations can occur in pulmonary hypertension, pulmonary embolism, renal insufficiency, and sepsis, reflecting ventricular stress but not necessarily primary heart failure 1. Always correlate with clinical context.
Medication Considerations
- NT-proBNP is NOT affected by neprilysin inhibitors (sacubitril/valsartan) and can be used without adjustments 1
- BNP levels should not be used to monitor treatment response with neprilysin inhibitors 1
Heart Failure with Preserved Ejection Fraction (HFpEF)
NT-proBNP levels are generally lower in HFpEF than in reduced ejection fraction heart failure, but the same diagnostic thresholds apply (NT-proBNP <125 pg/mL excludes HFpEF) 1, 5.
Clinical Decision Algorithm
If NT-proBNP <125 pg/mL (or <300 pg/mL in acute settings): Heart failure is effectively ruled out with 99% confidence 1, 5
If NT-proBNP is in the gray zone (300-900 pg/mL): Apply patient-specific adjustments for obesity, age, atrial fibrillation, renal function, and race; integrate with clinical assessment and consider echocardiography 2, 1
If NT-proBNP exceeds age-adjusted inclusion thresholds: Heart failure is highly likely; proceed with comprehensive cardiac evaluation 2, 1
If NT-proBNP is >4 times the normal range: 95% of patients have significant cardiovascular disease; the remainder typically have renal dysfunction 6